The proposed research concerns a detailed investigation of the physiological import of the pyridine nucleotide transhydrogenases in the essentially anaerobic, mitochondrial, energy generating processes of the adult parasitic helminths. Numerous helminths have been demonstrated to accumulate succinate as a major product of glucose catabolism and succinate formation is the result of an anaerobic, electron transport coupled, energy generating, intramitochondrial reduction of fumarate. Evidence obtained thus far indicates that the helminthic transhydrogenases serve to link the anaerobic utilization of the mitochondrial substrate, malate, with the ATP generating, electron transport system which results in fumarate reduction. The studies in progress and proposed will permit an evaluation of the transhydrogenase systems to ascertain the mechanism(s) involved in the coupling of these enzymes with electron transport and the metabolic role(s) of these enzymes in regulating anaerobic energy generation using adult Hymenolepis diminuta as a model. In addition, other helminthic systems are being evaluated. Since energy generation in the helminths appears strikingly different from that of their mammalian hosts, an understanding of helminthic energy generating systems is of great value in the search for potential, specific chemotherapeutic attack sites and the transhydrogenases may well serve as such sites.